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Preventing Pulmonary Complications in Surgical Patients at Risk of COVID-19 (PROTECT-Surg)

Primary Purpose

Pulmonary Complications in Surgical Patients, COVID, Severe Acute Respiratory Syndrome

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
RESP301
Sponsored by
University of Birmingham
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Pulmonary Complications in Surgical Patients focused on measuring Surgery, Pneumonia, COVID 19, COVID, SARS-Cov-2, SARS

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients aged 18 years and over. (This criteria MUST be made country-specific)
  • Planned to undergo abdominal or thoracic elective or emergency inpatient surgery requiring general anaesthesia.
  • Asymptomatic of COVID-19, including patients with: those not tested, negative test results, positive test but no symptoms (to be monitored post-surgery for symptoms)
  • Informed patient consent.
  • Able to operate a vibrating mesh nebuliser, as assessed by the recruiting physician

Exclusion Criteria:

  • Procedures under local anaesthesia
  • Known history of adverse reaction/contraindication to trial drug
  • Pregnancy and/or lactating patients (including patients undergoing caesarean section)
  • History of methaemoglobinaemia
  • Patients receiving any type of prescribed nitric oxide-donating agents (e.g. Nitroprusside, Isosorbide dinitrate, Isosorbide mononitrate, Naproxcinod, Molsidomine and Linsidomine)
  • Unable to tolerate use of a nebuliser and/or deemed unlikely to be able to adhere to protocol in view of investigator

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    No Intervention

    Experimental

    Arm Label

    Control (normal practice)

    RESP301

    Arm Description

    Treatment without the trial intervention. Patients will be treated as per hospital routine practice. The control arm may change over the course of the trial and will be monitored by the TMG and DMC

    RESP301 is administered quickly (8-10 minutes) via an easy-to-use, vibrating mesh nebuliser. The recommended nebulisers used to administer this intervention are available in all participating countries. The intervention will be administered using a nebuliser according to standard local practice; where permitted for patients to self-administer, a member of the clinical team will ensure that the patient has viewed the intervention administration training video, and will also oversee the patient for the first trial dose to ensure proper administration.

    Outcomes

    Primary Outcome Measures

    Pneumonia free survival; acute respiratory distress syndrome (ARDS) free survival; or death
    The primary outcome is any one of the following, inpatient, postoperative pulmonary complications: Pneumonia Acute respiratory distress syndrome (ARDS) Death

    Secondary Outcome Measures

    Rate of Pneumonia
    Pneumonia will be presented and analysed separately as a secondary outcome measure as well as within the composite primary outcome measure.
    Rate of ARDs
    ARDs will be presented and analysed separately as a secondary outcome measure
    Death rate
    Death will be presented and analysed separately as a secondary outcome measure
    Rate of unexpected ventilation
    Unexpected inability to extubate and wean patient from ventilation after general anaesthesia, or reintubation and ventilation by 30 days after surgery
    COVID-19 pulmonary complications
    Postoperative diagnosis of proven COVID-19 pulmonary complications
    Duration of hospital stay
    Duration of hospital stay (including time spent in intensive care, time ventilated)
    Pulmonary function
    Pulmonary function in keeping with the World Health Organisation (WHO) Solidarity Trial outcome scale

    Full Information

    First Posted
    April 30, 2020
    Last Updated
    August 25, 2021
    Sponsor
    University of Birmingham
    Collaborators
    Christian Medical College and Hospital, Ludhiana, India, Tamale Teaching Hospital, Ghana., University of Lagos, Nigeria, Kigali University Teaching Hospital, Hospital Español Veracruz, Université d'Abomey-Calavi, University of Witwatersrand, South Africa, University of Edinburgh, Istituto Clinico Humanitas, University of Cape Town
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04386070
    Brief Title
    Preventing Pulmonary Complications in Surgical Patients at Risk of COVID-19
    Acronym
    PROTECT-Surg
    Official Title
    Preventing Pulmonary Complications in Surgical Patients at Risk of COVID-19
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2021
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 1, 2021 (Anticipated)
    Primary Completion Date
    May 30, 2022 (Anticipated)
    Study Completion Date
    May 14, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University of Birmingham
    Collaborators
    Christian Medical College and Hospital, Ludhiana, India, Tamale Teaching Hospital, Ghana., University of Lagos, Nigeria, Kigali University Teaching Hospital, Hospital Español Veracruz, Université d'Abomey-Calavi, University of Witwatersrand, South Africa, University of Edinburgh, Istituto Clinico Humanitas, University of Cape Town

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The aim of this study is to reduce pulmonary complications in adult patients undergoing abdominal or thoracic surgery in COVID-19 exposed hospital environments. A Trial in Low and Middle Income Countries (LMICs)
    Detailed Description
    This trial has an adaptive platform design to identify at the earliest opportunity intervention arms which are showing benefit, drop arms which have a clear lack of benefit, and rapidly introduce new therapeutic options to the platform. This will enable rapid feedback of results to clinicians, allowing the standard of care to be modified as the pandemic progresses. Regular and frequent monitoring of results will be guided by an experienced, independent DMC. Eligible patients will be randomised at the level of the individual in a 1:1 ratio between: A. Control (normal practice) B. RESP301 6ml mixture of 150mM sodium nitrate, 50mM mannitol and 100mM citric acid, buffered at pH 5.4, three times per day (at least 4 hours apart), for 7 days or until discharge, whichever occurs first

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Pulmonary Complications in Surgical Patients, COVID, Severe Acute Respiratory Syndrome
    Keywords
    Surgery, Pneumonia, COVID 19, COVID, SARS-Cov-2, SARS

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Model Description
    The trial uses a Bayesian adaptive platform design, allowing for termination of arms if their superiority to standard care is established, and addition of new treatment arms. Patients will be randomised 1:1 to (A) Control (normal practice), (B) RESP301
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    6400 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Control (normal practice)
    Arm Type
    No Intervention
    Arm Description
    Treatment without the trial intervention. Patients will be treated as per hospital routine practice. The control arm may change over the course of the trial and will be monitored by the TMG and DMC
    Arm Title
    RESP301
    Arm Type
    Experimental
    Arm Description
    RESP301 is administered quickly (8-10 minutes) via an easy-to-use, vibrating mesh nebuliser. The recommended nebulisers used to administer this intervention are available in all participating countries. The intervention will be administered using a nebuliser according to standard local practice; where permitted for patients to self-administer, a member of the clinical team will ensure that the patient has viewed the intervention administration training video, and will also oversee the patient for the first trial dose to ensure proper administration.
    Intervention Type
    Drug
    Intervention Name(s)
    RESP301
    Intervention Description
    RESP301 is a formulation consisting of three agents already used in clinical practice: mannitol, sodium nitrite and citric acid. Delivered by a vibrating mesh nebuliser three times per day (TID) (at least 4 hours apart), for 7 days. Each dose of RESP301 is a 6ml admixture of 150mM NaNO2, 50mM mannitol and 100mM citric acid, buffered at pH 5.4.
    Primary Outcome Measure Information:
    Title
    Pneumonia free survival; acute respiratory distress syndrome (ARDS) free survival; or death
    Description
    The primary outcome is any one of the following, inpatient, postoperative pulmonary complications: Pneumonia Acute respiratory distress syndrome (ARDS) Death
    Time Frame
    From randomisation until discharge from hospital, average less than 30 days
    Secondary Outcome Measure Information:
    Title
    Rate of Pneumonia
    Description
    Pneumonia will be presented and analysed separately as a secondary outcome measure as well as within the composite primary outcome measure.
    Time Frame
    From randomisation until discharge from hospital, average less than 30 days
    Title
    Rate of ARDs
    Description
    ARDs will be presented and analysed separately as a secondary outcome measure
    Time Frame
    From randomisation until discharge from hospital, average less than 30 days
    Title
    Death rate
    Description
    Death will be presented and analysed separately as a secondary outcome measure
    Time Frame
    From randomisation until discharge from hospital, average less than 30 days
    Title
    Rate of unexpected ventilation
    Description
    Unexpected inability to extubate and wean patient from ventilation after general anaesthesia, or reintubation and ventilation by 30 days after surgery
    Time Frame
    From operation until 30 days post operation
    Title
    COVID-19 pulmonary complications
    Description
    Postoperative diagnosis of proven COVID-19 pulmonary complications
    Time Frame
    30 days post-surgery
    Title
    Duration of hospital stay
    Description
    Duration of hospital stay (including time spent in intensive care, time ventilated)
    Time Frame
    30 days post-surgery
    Title
    Pulmonary function
    Description
    Pulmonary function in keeping with the World Health Organisation (WHO) Solidarity Trial outcome scale
    Time Frame
    30 days post-surgery

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patients aged 18 years and over. (This criteria MUST be made country-specific) Planned to undergo abdominal or thoracic elective or emergency inpatient surgery requiring general anaesthesia. Asymptomatic of COVID-19, including patients with: those not tested, negative test results, positive test but no symptoms (to be monitored post-surgery for symptoms) Informed patient consent. Able to operate a vibrating mesh nebuliser, as assessed by the recruiting physician Exclusion Criteria: Procedures under local anaesthesia Known history of adverse reaction/contraindication to trial drug Pregnancy and/or lactating patients (including patients undergoing caesarean section) History of methaemoglobinaemia Patients receiving any type of prescribed nitric oxide-donating agents (e.g. Nitroprusside, Isosorbide dinitrate, Isosorbide mononitrate, Naproxcinod, Molsidomine and Linsidomine) Unable to tolerate use of a nebuliser and/or deemed unlikely to be able to adhere to protocol in view of investigator
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Donna Smith
    Phone
    +44 (0)121 415 9103
    Email
    PROTECT-Surg@trials.bham.ac.uk
    First Name & Middle Initial & Last Name or Official Title & Degree
    Rachel Lillywhite
    Phone
    +44 (0)121 414 4762
    Email
    PROTECT-Surg@trials.bham.ac.uk
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Aneel Bhangu
    Organizational Affiliation
    University of Birmingham
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    Hospital-level data will not be released or published. Country-level analyses will only be conducted with permission of lead investigators from each participating country. Local investigators may access their data across their country to perform country-level analyses (all participating hospitals should consent to their data being used in this way).
    Citations:
    PubMed Identifier
    34473343
    Citation
    Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
    Results Reference
    derived

    Learn more about this trial

    Preventing Pulmonary Complications in Surgical Patients at Risk of COVID-19

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